IthaID: 1094
Names and Sequences
| Functionality: | Globin gene causative mutation | Pathogenicity: | Pathogenic / Likely Pathogenic |
|---|---|---|---|
| Common Name: | CD 89 AGT>AGR [Ser>Arg] | HGVS Name: | HBB:c.270T>R |
| Hb Name: | Hb Vanderbilt | Protein Info: | β 89(F5) Ser>Arg |
| Also known as: |
We follow the
HGVS sequence variant nomenclature
and
IUPAC standards.
Context nucleotide sequence:
AAGGGCACCTTTGCCACACTGAG [T>R] GAGCTGCACTGTGACAAGCTGCA (Strand: -)
Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLRELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
Comments: Hb Vanderbilt ([β89(F5)Ser>Arg) has a high oxygen affinity and is observed together with polycythaemia in heterozygous individuals. It was initially detected by peptide mapping and sequence analysis, but was later reported by direct sequencing to be the result of two possible substitutions leading to the same amino acid change (AGT>AGG or AGT>AGA). The abnormal Hb can not be detected by conventional electrophoresis, but is separated from Hb A using anion exchange chromatography. It has reduced sensitivity to 2,3-diphosphoglycerate acid (2,3-DPG), possibly due to conformational change in its binding site, thereby increasing Hb affinity for oxygen.
Phenotype
| Hemoglobinopathy Group: | Structural Haemoglobinopathy |
|---|---|
| Hemoglobinopathy Subgroup: | β-chain variant |
| Allele Phenotype: | N/A |
| Stability: | N/A |
| Oxygen Affinity: | Increased Oxygen Affinity |
| Associated Phenotypes: | N/A |
Location
| Chromosome: | 11 |
|---|---|
| Locus: | NG_000007.3 |
| Locus Location: | 70994 |
| Size: | 1 bp |
| Located at: | β |
| Specific Location: | Exon 2 |
Other details
| Type of Mutation: | Point-Mutation(Substitution) |
|---|---|
| Effect on Gene/Protein Function: | Missense codons (Protein Structure) |
| Ethnic Origin: | Caucasian, Polish |
| Molecular mechanism: | N/A |
| Inheritance: | Dominant |
| DNA Sequence Determined: | Yes |
In silico pathogenicity prediction
Publications / Origin
- Paniker NV, Lin KT, Krantz SB, Flexner JM, Wasserman BK, Puett D, Haemoglobin Vanderbilt (alpha2beta289Ser leads to Arg): a new haemoglobin with high oxygen affinity and compensatory erythrocytosis., British journal of haematology, 39(2), 249-58, 1978
- Goodyer MJ, Elhassadi EI, Percy MJ, McMullin MF, A novel base change leading to Hb Vanderbilt [β89(F5)Ser→Arg, AGT>AGA]., Hemoglobin , 35(4), 428-9, 2011
- Shomali W, Brar R, Arekapudi SR, Gotlib JR, A Kindred with a β-Globin Base Substitution [β89(F5)Ser→Arg (AG>AG); : c.270T>G] Resulting in Hemoglobin Vanderbilt., Hemoglobin, 43(0), 273-276, 2019